Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication

PLoS Pathogens

Jonah B. Sacha¹  David H. O’Connor²  Roger W. Wiseman³  Sarah R. DiNapoli³  Benjamin J. Burwitz³  Connor R. Buechler³  Gabrielle Lehrer-Brey³  Mariel S. Mohns³  Jason T. Weinfurter³  Adam J. Ericsen³  Kristin A. Crosno³  James P. Mutschler⁴  Jacob D. Estes⁵  Thomas C. Friedrich⁵  Michael Lauck⁶  Justin M. Greene⁷  Jason M. Brenchley⁷  Eric J. Peterson⁷  Trent M. Prall⁷  Matthew R. Reynolds⁷  Samantha M. Gieger⁷ 

[1] AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, United States Of America;Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America;Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America;Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States Of America;Vaccine & Gene Therapy Institute, Oregon National Primate Research Center, and Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States Of America;Virology Training Program, University of Wisconsin-Madison, Madison, Wisconsin, United States Of America;Wisconsin National Primate Research Center, Madison, Wisconsin, United States Of America

关键词: Macaque;    Blood plasma;    SIV;    Viremia;    Gastrointestinal infections;    HIV infections;    Viral replication;    Inflammation;   

DOI  :  10.1371/journal.ppat.1006048

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute “pre-peak” phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood. This, heretofore unappreciated, hyperacute-phase microbial translocation was accompanied by sustained reduction of lipopolysaccharide (LPS)-specific antibody titer, intestinal permeability, increased abundance of CD4+CCR5+ T cell targets of virus replication, and T cell activation. To test whether increasing gastrointestinal permeability to cause microbial translocation would amplify viremia, we treated two SIV-infected macaque ‘elite controllers’ with a short-course of dextran sulfate sodium (DSS)–stimulating a transient increase in microbial translocation and a prolonged recrudescent viremia. Altogether, our data implicates translocating microbes as amplifiers of immunodeficiency virus replication that effectively undermine the host’s capacity to contain infection.

【 授权许可】

CC BY